This program is designed to provide a multifaceted approach to the study of the physiological significance of blood rheology studies. The long range goal of the proposed research is to contribute to the understanding of the relation of the rheological properties of blood to: 1) the flow of blood in vivo; 2) the diagnosis and treatment of clinical disorders associated with potential rheological disorders. The specific aims of the present program include: 1) systematic studies of red blood cell (RBC) aggregation induced by proteins and various polymers (e.g., poloxamers, PEGs) in solution or attached to the RBC surface in order to more clearly detail the mechanism(s) of RBC aggregation; 2) continued investigation of specific RBC cellular factors which influence RBC aggregation and thus to explore reasons for differences in aggregation such as those associated with cell age or between red cells from healthy donors; 3) cooperative studies with Dr. Paul C. Johnson (University of California, San Diego) in which poloxamer-coated rat RBC will be utilized in his in vivo rat spinotrapezius muscle preparation in order to determine plasma viscosity-RBC aggregation interactions for selected microvascular flow parameters (i.e., velocity profiles, aggregate dimensions, formation of aggregates); 4) hemorheological evaluation of blood, red cells and white cells from patients whose clinical state is characterized by altered rheological properties of blood (e.g., hypertension, sepsis). Successful completion of the major aims of this program should provide: 1) greater insight into the process of RBC aggregation and the role of cellular factors versus suspending media properties in this phenomenon; 2) quantitative information relevant to the effects of elevated RBC aggregation and plasma viscosity on muscle microvascular blood flow; 3) detailed data regarding the macro- and micro-rheological properties of pathologic blood and the extent to which rheological abnormalities are affected by metabolic state, therapy, and clinical status. Of long range significance is the potential contribution which studies of this type may make to clinical medicine: if the terms "hyperviscosity" or "hyperviscosity syndrome" are to be utilized with scientific meaning, a clearer understanding of their etiology, rheologic mechanisms and physiological importance is essential.